Evidence map›Paper›PMID 25012994›Full record

Trial reportCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2014

Known and novel sources of variability in the nicotine metabolite ratio in a large sample of treatment-seeking smokers.

Meghan J Chenoweth, Maria Novalen, Larry W Hawk, Robert A Schnoll, Tony P George, Paul M Cinciripini, Caryn Lerman, Rachel F Tyndale

Registry-linked trialOpen access · greenAbstract readClinical Trial
In one paragraph

Trial report in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01314001 (Pharmacogenetics of Nicotine Addiction Treatment), which is not on this map. Cited by 85 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 5 pooled it
6.8field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01314001 phase3completednot on this map

Pharmacogenetics of Nicotine Addiction Treatment (PNAT)

TypeinterventionalSponsorUniversity of PennsylvaniaRan2010 to 2014Enrolled1,246ConditionsNicotine AddictionArmsVarenicline, Placebo, Transdermal Nicotine
3 · Its place in the literature

Who cites it

85 citing papers in PubMed, 5 syntheses or guidelines pooled it, 120 citations in OpenAlex.

  1. Nicotine receptor partial agonists for smoking cessation.The Cochrane database of systematic reviews · 2023
    Pooled it
  2. Nicotine Metabolism Predicted by CYP2A6 Genotypes in Relation to Smoking Cessation: A Systematic Review.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022
    Pooled it
  3. Pooled it
  4. Nicotine receptor partial agonists for smoking cessation.The Cochrane database of systematic reviews · 2016
    Pooled it
  5. Sex Differences in Varenicline Efficacy for Smoking Cessation: A Meta-Analysis.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016
    Pooled it
  6. Trial
  7. Trial
  8. Relationships Between the Nicotine Metabolite Ratio and Laboratory Assessments of Smoking Reinforcement and Craving Among Adults in a Smoking Cessation Trial.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024
    Trial
  9. Trial
  10. Trial
  11. Trial
  12. Pregnancy-Induced Increases in the Nicotine Metabolite Ratio: Examining Changes During Antepartum and Postpartum.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2019
    Trial
  13. Trial
  14. Trial
  15. Trial
  16. The Nicotine Metabolite Ratio is Associated With Early Smoking Abstinence Even After Controlling for Factors That Influence the Nicotine Metabolite Ratio.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016
    Trial
  17. Nicotine Metabolite Ratio Is Associated With Lozenge Use But Not Quitting in Smokeless Tobacco Users.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2016
    Trial
  18. Test-Retest Reliability and Stability of the Nicotine Metabolite Ratio Among Treatment-Seeking Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2015
    Trial
  19. Trial
  20. Article

25 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

Meghan J ChenowethCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Maria NovalenCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
Larry W HawkDepartment of Psychology and Center for Children and Families, University at Buffalo, SUNY, Buffalo, New York.
Robert A SchnollDepartment of Psychiatry, Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania, Philadelphia, Pennsylvania.
Tony P GeorgeCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. Division of Brain and Therapeutics, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada.
Paul M CinciripiniDepartment of Behavioral Science, University of Texas MD Anderson Cancer Center, Houston, Texas.
Caryn LermanDepartment of Psychiatry, Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania, Philadelphia, Pennsylvania.
Rachel F TyndaleCampbell Family Mental Health Research Institute, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada. Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. r.tyndale@utoronto.ca.
University of Toronto · CA

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
UNIVERSITY OF PENNSYLVANIA CAN CTR SUPPORT GRANTP30CA016520 · NCI · UNIVERSITY OF PENNSYLVANIA · PI Robert H. Vonderheide · 1985 to 2026
$222.3M
University of Toronto Coordinating Genetics Core & Clinical Trial SiteU01DA020830 · NIDA · UNIVERSITY OF PENNSYLVANIA · PI LERMAN, CARYN, TYNDALE, RACHEL FYNVOLA · 2005 to 2014
$22.4M
CIHR MOP86471NCI NIH HHS P30 CA016520NCI NIH HHS P30 CA016672NIDA NIH HHS DA020830NIDA NIH HHS U01 DA020830
6 · The paper itself

Abstract

backgroundThe ratio of 3'hydroxycotinine to cotinine, or nicotine metabolite ratio (NMR), is strongly associated with CYP2A6 genotype, CYP2A6-mediated nicotine and cotinine metabolism, and nicotine clearance. Higher NMR (faster nicotine clearance) is associated retrospectively with heavier smoking and lower cessation rates.

methodsNMR as a predictive biomarker of cessation outcomes is being investigated (NCT01314001). In addition to strong CYP2A6 genetic influences on NMR, demographic and hormonal factors alter NMR. Here, we analyzed, for the first time together, these sources of variation on NMR in smokers screened for this clinical trial (N = 1,672).

resultsParticipants (mean age = 45.9) were 65.1% Caucasian, 34.9% African American, and 54.8% male. Mean NMR (SD) was higher in Caucasians versus African Americans [0.41 (0.20) vs. 0.33 (0.21); P < 0.001], and in females versus males [0.41 (0.22) vs. 0.37 (0.20); P < 0.001]. Among females, birth control pill use (N = 17) and hormone replacement therapy (N = 14) were associated with 19.5% (P = 0.09) and 29.3% (P = 0.06) higher mean NMR, respectively, albeit nonsignificantly. BMI was negatively associated with NMR (Rho = -0.14; P < 0.001), whereas alcohol use (Rho = 0.11; P < 0.001) and cigarette consumption (Rho = 0.12; P < 0.001) were positively associated with NMR. NMR was 16% lower in mentholated cigarette users (P < 0.001). When analyzed together in a linear regression model, these predictors (each ≤2%) accounted for <8% of total NMR variation.

conclusionsAlthough these factors significantly affected NMR, they contributed little (together <8%; each ≤2%) to total NMR variation. IMPACT: Thus, when using NMR, for example, to prospectively guide smoking cessation therapy, these sources of variation are unlikely to cause NMR misclassification.

Indexed as

CotinineCytochrome P-450 CYP2A6FemaleGenotypeHumansLinear ModelsMaleMiddle AgedNicotinePredictive Value of TestsSmokingSmoking CessationTobacco Use DisorderCotinineCYP2A6 protein, humanCytochrome P-450 CYP2A6hydroxycotinineNicotine

Identifiers

PMID25012994
PMCPMC4154993
OpenAlexW2102370119

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.